Transcript

Norman Swan: As Tony Broe said, many things are known to increase the changes of dementia, from not going far in the education system, to coronary risk factors, to head injury. But could it be that common mental health issues such as depression somehow affect the brain to the extent that thinking and memory are damaged permanently. That's what a recent study led by Archana Singh-Manoux sought to answer. Archana is a research professor at INSERM in France and professor of epidemiology at University College London.

Archana Singh-Manoux: There's been a lot of research looking at whether depression is a risk factor for dementia. Most studies on dementia are based on older adults, these are people who are 65 and older who were followed until they develop dementia. And the results are mixed, inconsistent, with some studies suggesting that depression increases the risk of dementia and other studies not finding an association. So what we wanted to do was to take a slightly different approach. We said, okay, we've got data on depressive symptoms, up to 3 decades before the diagnosis of dementia. So we want to see how are these two related. So what we've really done is to look at symptoms of depression through these three decades leading up to dementia, to figure out whether there is some sort of a causal association between the two.

Norman Swan: And the study you use is called the Whitehall II study, which is a famous study of civil servants in the British civil service, and we've often spoken about this study on the Health Report in the past with Sir Michael Marmot because it is where he got his original data on in equities in health and the health gradient between the lowest levels in terms of education and income, and the highest levels of the civil service. So you used this follow-up group of people to actually dissect it for depression and dementia.

Archana Singh-Manoux: Absolutely. So the study was put together…I mean, Michael was a PI of the study, he set up a study in 1985, and it's based on about 10,000 people, civil servants, who have been followed since 1985. And although Michael remains involved in the study, he's got other things to do, so we've taken this on, and it has now become a study on ageing, simply because you see a range of cardiovascular, metabolic risk factors, health behaviours…

Norman Swan: You know a lot about these people.

Archana Singh-Manoux: We know a lot about these people because we know what happens to them and we've seen them every 3 to 4 years and then we've got data from the electronic health registers on a range of health outcomes. So it's really turned now into a study on ageing. The initial research question was definitely looking at social inequalities and how they come about and why they come about and what the extent of the inequalities are in various health outcomes.

Norman Swan: And so you measured depressive symptoms on nine occasions during that time, between 1985 and 2012, rather than a diagnosis of depression.

Archana Singh-Manoux: Yes, that's right. I mean, diagnosing depression is a little bit complicated. We had some data on people who had been hospitalised for depression in this cohort, but the main analysis was based on depressive symptoms. And that's what has been done in other studies. You know, we're not doing this differently. Some studies have looked at whether people take antidepressants and what the risk of dementia is, but most of the research evidence in this domain is symptoms of depression rather than clinical depression.

Norman Swan: So let's get to the money; what did you find?

Archana Singh-Manoux: Well, the good news is that depression isn't a risk factor really. If you look at people who have had depression in midlife, they have no increased risk of dementia, none at all. But what tends to happen is that before the onset of clinical dementia…

Norman Swan: So when you work back…so you've got somebody with dementia and you work back…

Archana Singh-Manoux: Yes, when we work back we see that in the 10 years leading up to this diagnosis there is an increase in depressive symptoms. There's many ways of looking at it. One would be that this is just people realising that their cognitive capacities are declining and depression is part of it…

Norman Swan: A reactive depression, in a sense.

Archana Singh-Manoux: Yes, a little bit, in a reverse causation of the jargon we use to explain this. But it's also possible that there are common processes which lead to both depressive symptoms and to dementia. But in both those scenarios, with both these interpretations, there is no real evidence that depression itself increases the risk of dementia, if you see what I mean. There's no real causal link. Our data do not support a causal link between the two.

Norman Swan: You call it in this study a prodrome, which is like a child getting a fever two days before the rash comes out of chickenpox or something like that, that's the prodrome, the period before…the symptomatic period before you actually declare the disease. So you're really saying it's part and parcel of the dementia, whether it's a reactive thing or part of the pathology.

Archana Singh-Manoux: Yes, absolutely. And we know…I mean, now there are other studies which has shown that the diagnosis of dementia is preceded by many changes over the course of 10, up to 20 years. Changes in the brain, changes in behaviour, the changes in personality, and then there are changes in affect. So if the association between depression and dementia seems to be driven by the changes, the pattern, the cascade of changes that are involved in dementia, rather than some sort of an association where you say, okay, if you're depressed your risk of dementia is higher.

Norman Swan: So if you have depression in midlife, it is not something to be depressed about, you shouldn't be depressed about the fact that you think this is inevitable you're going to get dementia, because it's not. Karen Ritchie in Montpellier, an Australian researcher who has worked there for many years, reckons that you actually can find evidence of dementia in various ways, almost like this prodrome, decades before you develop it. Have you looked at that, whether there's a feature…when you work back from the people you now know in the Whitehall study who have got dementia, are there things that are signposts to dementia that could be detected perhaps in midlife that aren't depression?

Archana Singh-Manoux: Absolutely. This revealed that dementia is not something that happens just in old age, it involves changes over a long, long period. A lot of people now increasingly believe that. And in our own study we're beginning to look at a range of other things. We are looking at changes in weight, we're looking at changes in cognitive function. We show decline in cognitive function again in the 10 to 15 years before dementia diagnosis. So if we match people for age and socio-economic position and education, those who get dementia have a rapid decline in cognitive ability.

But it's not just cognition. For instance, there's also weight loss. There are other changes. But all these findings show, and these are all recent findings, what they suggest is that something we thought was a disease of the old, dementia, it actually is something that unfolds over a long period of time. That's problematic in terms of when you're looking at what the risk and protective factors are. It's a little bit problematic to try and tease apart things that cause dementia from risk factors that are just part of the dementia process. So it complicates our life a little bit, knowing that the disease unfolds over such a long period.

Norman Swan: And returning to depression for a moment, because the important thing is intervention points. Is there any evidence, when you look at what people were given for treatment and so on, that in the five or 10 years before you develop dementia in this prodrome period, that treating the dementia symptoms made any difference to the outcome?

Archana Singh-Manoux: Studies haven't looked at that specific research question, but I think that's a really interesting thing one must look at. I mean, it can be done in intervention studies, you know, you can look at people who have had mild cognitive impairment and depression, and assess whether treating the depression would delay the clinical onset of dementia. It might not change the disease in the brain but it might just mean that you have a little more time, one or two years, three years, four years, more, before you have the chemical symptoms of depression. A study like ours can't look at this, we're an observational study, we can't look at this. But I think this is a very interesting area of research where we said, okay, what are the things we can do, what are the interventions that we can do to just delay the onset of dementia. And I'm sure there will be people who will be running such studies to come up with results in this domain.

Norman Swan: But the overarching message from this is that the study of dementia to find out more about it is really a long game, it's not actually one that is much helped by looking at people with dementia itself, you've got to look several years ahead.

Archana Singh-Manoux: That's something we've been saying for a long, long time. You know that the other thing that people don't think about is that all the medication that has been tested, all the molecules that have been tested to cure or delay onset, they've all failed. It's one area of research which has a failure rate of 100%, 99.6% or whatever, I mean, nothing works. So we've got to start thinking about this differently, and I think part of the answer lies in looking and accepting that this is a disease which really is a long-term disease. So when we're looking at risk factors, trying to identify risk factors, we want to keep that in mind because short studies that have a short follow-up of a few years, five years, six years, may come up with answers that are just wrong.

Norman Swan: Archana, thank you very much for joining us on the Health Report.

Archana Singh-Manoux: Thank you very much.

Norman Swan: Archana Singh-Manoux is a research professor at INSERM in France and a professor of epidemiology at University College London.